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Hypertension and NAFLD risk: Insights from the NHANES 2017-2018 and Mendelian randomization analyses.
Yuan, M, He, J, Hu, X, Yao, L, Chen, P, Wang, Z, Liu, P, Xiong, Z, Jiang, Y, Li, L
Chinese medical journal. 2024;(4):457-464
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Abstract
BACKGROUND Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and Mendelian randomization (MR) analyses. METHODS Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017-2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results. RESULTS A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159-2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis ( β = 7.836 [95% CI, 2.334-13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297-22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003-1.046]), DBP (OR = 1.047 [95% CI, 1.005-1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05). CONCLUSION Hypertension was associated with an increased risk of NAFLD.
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Association between body fat composition and hyperhomocysteinemia in the analysis of the baseline data of the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX).
Liu, W, Li, Q, Wang, Q, Ma, S, Yang, X, Zhang, J, Qiu, J, Li, J, Yang, C, Li, X, et al
Journal of clinical hypertension (Greenwich, Conn.). 2023;(6):573-581
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Abstract
The authors conducted an observational study to explore the association between body fat composition and the risk of hyperhomocysteinemia (HHcy) and their combined effect on the risk of developing cardiovascular disease (CVD). Adults aged 18-74 years from the Northwest China Natural Population Cohort: Ningxia Project (CNC-NX) were recruited in this study. Association between body fat composition and HHcy was evaluated by logistic regression model. Restricted cubic spline was used to find nonlinear association. The impact of the interaction between HHcy and body fat composition on CVD was evaluated using the addition interaction model and mediation effect model. In total, 16 419 participants were included in this research. Body fat percentage, visceral fat level, and abdominal fat thickness were positively associated with overall HHcy (p for trend < .001). Adjusted odds ratios (ORs) in quarter 4 were 1.181 (95% CI: 1.062, 1.313), 1.202 (95% CI: 1.085, 1.332), and 1.168 (95% CI: 1.055, 1.293) for body fat percentage, visceral fat level, and abdominal fat thickness, respectively, compared with those in quarter 1. Subgroup analysis indicated age, estimated glomerular filtration rate (eGFR), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and CVD were the interaction factors of body fat percentage, visceral fat level, abdominal fat thickness with HHcy (all p for interaction < .05). ORs of CVD were higher in participants with HHcy and high body fat. Body fat composition was positively associated with HHcy, indicating that reducing body, abdominal, and visceral fat content may lower the risk of HHcy and CVD.
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Investigating linear and nonlinear associations of LDL cholesterol with incident chronic kidney disease, atherosclerotic cardiovascular disease and all-cause mortality: A prospective and Mendelian randomization study.
Wang, Z, Xiao, Y, Lu, J, Zou, C, Huang, W, Zhang, J, Liu, S, Han, L, Jiao, F, Tian, D, et al
Atherosclerosis. 2023;:117394
Abstract
BACKGROUND AND AIMS Observational studies suggest potential nonlinear associations of low-density lipoprotein cholesterol (LDL-C) with cardio-renal diseases and mortality, but the causal nature of these associations is unclear. We aimed to determine the shape of causal relationships of LDL-C with incident chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality, and to evaluate the absolute risk of adverse outcomes contributed by LDL-C itself. METHODS Observational analysis and one-sample Mendelian randomization (MR) with linear and nonlinear assumptions were performed using the UK Biobank of >0.3 million participants with no reported prescription of lipid-lowering drugs. Two-sample MR on summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen (N = 625,219) was employed to replicate the relationship for kidney traits. The 10-year probabilities of the outcomes was estimated by integrating the MR and Cox models. RESULTS Observationally, participants with low LDL-C were significantly associated with a decreased risk of ASCVD, but an increased risk of CKD and all-cause mortality. Univariable MR showed an inverse total effect of LDL-C on incident CKD (HR [95% CI]:0.84 [0.73-0.96]; p = 0.011), a positive effect on ASCVD (1.41 [1.29-1.53]; p<0.001), and no significant causal effect on all-cause mortality. Multivariable MR, controlling for high-density lipoprotein cholesterol (HDL-C) and triglycerides, identified a positive direct effect on ASCVD (1.32 [1.18-1.47]; p<0.001), but not on CKD and all-cause mortality. These results indicated that genetically predicted low LDL-C had an inverse indirect effect on CKD mediated by HDL-C and triglycerides, which was validated by a two-sample MR analysis using summary-level data from the Global Lipid Genetics Consortium (N = 296,680) and the CKDGen consortium (N = 625,219). Suggestive evidence of a nonlinear causal association between LDL-C and CKD was found. The 10-year probability curve showed that LDL-C concentrations below 3.5 mmol/L were associated with an increased risk of CKD. CONCLUSIONS In the general population, lower LDL-C was causally associated with lower risk of ASCVD, but appeared to have a trade-off for an increased risk of CKD, with not much effect on all-cause mortality. LDL-C concentration below 3.5 mmol/L may increase the risk of CKD.
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Impact of CD4+ T-cell count on sustained virologic response to direct-acting antivirals in hepatitis C virus monoinfected cancer patients: a prospective observational study.
Angelidakis, G, Pritchard, H, Yibirin, M, Jiang, Y, Mustafayev, K, Torres, HA
Diagnostic microbiology and infectious disease. 2022;(3):115719
Abstract
Limited data are available on the use of CD4+ T-cell count and percentage to predict response to direct-acting antiviral (DAA) treatment outside the hepatitis C virus (HCV)-HIV coinfected population. We sought to determine the impact of CD4+ T-cell count and percentage on response to DAAs in cancer patients with HCV monoinfection. Patients treated with DAAs were enrolled in a prospective observational study. CD4+ T-cell count and percentage was measured at baseline, end of treatment (EOT), and 12 weeks after the EOT (SVR12). A total of 174 patients were enrolled. Most patients (155/174, 89%) achieved an SVR12. A multivariate logistic regression model found that patients with hepatocellular carcinoma, HCV-3 and previous DAA treatment were more likely to develop treatment failure. Neither univariate analysis nor multivariate logistic regression analysis did show any association between CD4+ T-cell count or percentage and SVR12. CD4 T-cell count or percentage does not appear to impact SVR rates in cancer patients with HCV monoinfection receiving DAAs.
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Non-Invasive Detection of Fetal Vascular Endothelial Function in Gestational Diabetes Mellitus.
Chen, Y, Huang, D, Liu, J, Zeng, F, Tang, G, Lei, W, Wang, H, Jiang, Y, Shentu, W, Wang, H
Frontiers in endocrinology. 2021;:763683
Abstract
OBJECTIVES Endothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers. METHODS This observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared. RESULTS vWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P < 0.05). There was a moderate but significant correlation between APV and vWF (r =-0.58, P < 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index. CONCLUSIONS Color M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.
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Ceramide subclasses identified as novel lipid biomarker elevated in women with polycystic ovary syndrome: a pilot study employing shotgun lipidomics.
Jiang, Y, Qi, J, Xue, X, Huang, R, Zheng, J, Liu, W, Yin, H, Li, S
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2020;(6):508-512
Abstract
This study aimed to identify potential lipid biomarkers in women with polycystic ovary syndrome (PCOS) and determine their predictive value for PCOS. Eighteen women with PCOS and 17 healthy controls were enrolled. A multi-dimensional mass spectrometry-based shotgun lipidomics approach was employed to analyze serum lipid profiles. Shotgun lipidomics revealed that the concentrations of ceramide (Cer) and phosphatidylcholine (PC) were higher (PC: 831.6 ± 217.4 vs. 605.2 ± 164.2 μmol/l; Cer: 3,387.6 ± 829.9 vs. 2,552.2 ± 679.4 nmol/l, respectively), whereas that of lysophosphatidylcholine was lower, in PCOS women than in healthy controls (82.02 ± 39.49 vs. 133.62 ± 65.36 μmol/l, respectively). Receiver operating characteristic analysis showed that the combination of Cer (OH_N16:0/N18:0) and Cer (N22:0) had the greatest discriminatory power to differentiate between women with and without PCOS (area under the curve: 0.889, 95% confidence interval: 0.784-0.994). These results indicate that the combination of Cer (OH_N16:0/N18:0) and Cer (N22:0) may represent a novel lipid predictor of PCOS.
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Analysis of TATA-box binding protein associated factor 4b gene mutations in a Chinese population with nonobstructive azoospermia.
Xi, Q, Zhang, H, Zhang, X, Jiang, Y, Wang, R, Liu, R, Zhang, H
Medicine. 2020;(23):e20561
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Abstract
Nonobstructive azoospermia (NOA) is a severe form of male infertility. The molecular basis of NOA is still poorly understood. The aim of this study was to explore the associations between single nucleotide polymorphisms (SNPs) of the TATA-box binding protein associated factor 4b (TAF4B) gene and NOA. A total of 100 Han Chinese patients with NOA and 100 healthy men as controls were recruited. Targeted gene capture sequencing was performed. A total of 11 TAF4B SNPs were screened in the NOA and control subjects. Six synonymous and 4 nonsynonymous variants were detected. The c.11G>T (p.G4V) mutation was detected only in NOA patients. Polymorphism Phenotyping v2 and Sorting Intolerant From Tolerant analysis indicated that the p.G4V mutation influenced the protein structure of TAF4B. Haplotype analysis showed that the candidate SNPs did not independently associate with NOA and were found at extremely low frequencies in the subject population. Mutation Taster analysis indicated that the c.11G>T/p.G4V mutation was damaging. WebLogo analysis showed that the residue at amino acid 4 was relatively conserved. The p.Gly4Val substitution may affect the structure of the TAF4B protein. The c.11G>T mutation of the TAF4B gene may be associated with NOA in a Chinese population. Bioinformatics analysis indicated this variation may play an important role in the process of spermatogenesis.
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Sarcopenia associates with increased risk of hepatocellular carcinoma among male patients with cirrhosis.
Feng, Z, Zhao, H, Jiang, Y, He, Z, Sun, X, Rong, P, Wang, W
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3132-3139
Abstract
BACKGROUND & AIMS Sarcopenia is associated with a higher rate of complications and is an independent predictor of poor outcomes in cirrhosis. The aim of this study was to investigate the association between sarcopenia and the risk of hepatocellular carcinoma (HCC) among patients with cirrhosis. METHODS Four hundred and ninety-two patients with cirrhosis and no evidence of HCC from 2008 to 2017 were enrolled, who had baseline abdominal computed tomography (CT) analyzed for identification of sarcopenia according to the previously established sex-specific cutoffs. The main endpoint of follow-up was the occurrence of HCC. RESULTS The majority of patients were male (365/492, 74.2%), and sarcopenia were present in 238 (48.4%) patients at baseline. During a median follow-up of 3.6 years, 54 (11.0%) patients developed HCC. The cumulative incidence of HCC was significantly higher in male patients with sarcopenia than those without sarcopenia (P = 0.001), but not in female patients (P = 0.26). Multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.09-4.74) was a significant independent factor for HCC development in male patients with cirrhosis, which was consistently identified through competing-risk analysis (subdistribution HR, 2.20; 95% CI, 1.02-4.72). After propensity score matching, male cirrhotic patients with sarcopenia still had a higher risk of HCC than those without sarcopenia (P = 0.02). CONCLUSION Sarcopenia is associated with an increased risk of developing HCC among male patients with cirrhosis. Therefore, nutritional assessment and necessary interventions in specific cirrhotic patients need to be valued.
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Ultrasound characteristics of cervical lesions in patients with radioiodine refractory differentiated thyroid cancer: A strobe-compliant article.
Gao, L, Lin, Y, Jiang, Y, Li, H, Gao, Q, Xi, X, Wang, Y, Yang, X, Lai, X, Zhu, S, et al
Medicine. 2019;(45):e17876
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Abstract
Radioiodine refractory (RAIR) is the major cause of thyroid cancer-related death. In order to avoid needless Radioiodine (RAI) therapy, recognizing the RAIR cases in time is important for the patients to obtain more time for the effective therapy.Evaluate the ultrasound features of cervical metastatic lymph node in patients with RAIR differentiated thyroid cancer (DTC).Seventeen adult patients with histologically confirmed locally advanced or metastatic RAIR-DTC were prospectively enrolled. The ultrasound (US) characteristics of cervical lesions in patients with the RAIR-DTC were compared with cervical lymph node metastasis from 59 non RAIR-DTC cases.Among the 17 patients, cervical lymph node metastasis was found in 15 patients (88.3%). The cervical lesions of RAIR-DTC (mean size, 2.0 cm) were larger than that in non RAIR-DTC group (mean size, 1.30 cm). More multiple lesions and more lesions with visible flow were found in the RAIR Group, while fewer hyperechogenic punctuations were found in RAIR group (P < .05). The distant metastasis rates showed that RAIR-DTC led to a poorer prognosis than those of patients in the non RAIR Group (P < .01).Ultrasound can help distinguish metastasized cervical lymph nodes of RAIR-DTC patients from non RAIR-DTC patients. For RAIR-DTC patients, a long-term US evaluation should be performed.
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Sofosbuvir-Based Therapy in Hepatitis C Virus-Infected Cancer Patients: A Prospective Observational Study.
Torres, HA, Economides, MP, Angelidakis, G, Hosry, J, Kyvernitakis, A, Mahale, P, Jiang, Y, Miller, E, Blechacz, B, Naing, A, et al
The American journal of gastroenterology. 2019;(2):250-257
Abstract
BACKGROUND Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients. METHODS Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed. RESULTS We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%). CONCLUSIONS SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.